Wearable Sensors and Machine Learning for Hypovolemia Problems in Occupational, Military and Sports Medicine: Physiological Basis, Hardware and Algorithms

Hypovolemia is a physiological state of reduced blood volume that can exist as either (1) absolute hypovolemia because of a lower circulating blood (plasma) volume for a given vascular space (dehydration, hemorrhage) or (2) relative hypovolemia resulting from an expanded vascular space (vasodilation) for a given circulating blood volume (e.g., heat stress, hypoxia, sepsis). This paper examines the physiology of hypovolemia and its association with health and performance problems common to occupational, military and sports medicine. We discuss the maturation of individual-specific compensatory reserve or decompensation measures for future wearable sensor systems to effectively manage these hypovolemia problems. The paper then presents areas of future work to allow such technologies to translate from lab settings to use as decision aids for managing hypovolemia. We envision a future that incorporates elements of the compensatory reserve measure with advances in sensing technology and multiple modalities of cardiovascular sensing, additional contextual measures, and advanced noise reduction algorithms into a fully wearable system, creating a robust and physiologically sound approach to manage physical work, fatigue, safety and health issues associated with hypovolemia for workers, warfighters and athletes in austere conditions.

Quantification of stroke volume in a simulated healthy volunteer model of traumatic haemorrhage; a comparison of two non-invasive monitoring devices using error grid analysis alongside traditional measures of agreement

Introduction Haemorrhage is a leading cause of death following traumatic injury and the early detection of hypovolaemia is critical to effective management. However, accurate assessment of circulating blood volume is challenging when using traditional vital signs such as blood pressure. We conducted a study to compare the stroke volume (SV) recorded using two devices, trans-thoracic electrical bioimpedance (TEB) and supra-sternal Doppler (SSD), against a reference standard using trans- thoracic echocardiography (TTE). Methods A lower body negative pressure (LBNP) model was used to simulate hypovolaemia and in half of the study sessions lower limb tourniquets were applied as these are common in military practice and can potentially affect some haemodynamic monitoring systems. In order to provide a clinically relevant comparison we constructed an error grid alongside more traditional measures of agreement. Results 21 healthy volunteers aged 18–40 were enrolled and underwent 2 sessions of LBNP, with and without lower limb tourniquets. With respect to absolute SV values Bland Altman analysis showed significant bias in both non-tourniquet and tourniquet strands for TEB (-42.5 / -49.6 ml), rendering further analysis impossible. For SSD bias was minimal but percentage error was unacceptably high (35% / 48%). Degree of agreement for dynamic change in SV, assessed using 4 quadrant plots showed a seemingly acceptable concordance rate for both TEB (86% / 93%) and SSD (90% / 91%). However, when results were plotted on an error grid, constructed based on expert clinical opinion, a significant minority of measurement errors were identified that had potential to lead to moderate or severe patient harm. Conclusion Thoracic bioimpedance and suprasternal Doppler both demonstrated measurement errors that had the potential to lead to clinical harm and caution should be applied in interpreting the results in the detection of early hypovolaemia following traumatic injury.

Use of modern forensic methods for post-mortem diagnosis of blood loss

In forensic medical practice, when diagnosing the cause of death from blood loss, it is often necessary to solve questions related to the etiology of loss of circulating blood volume (CBV), the degree and severity of the injury, as well as its role in thanatogenesis and the duration of the terminal (agonal) period. When investigating the cases of death from acute blood loss, the authorities often ask forensic experts to solve issues related to the possibility of performing active targeted actions by the dying person, as well as to assess the timeliness of medical care and the actions of medical personnel. The solution of these issues is often difficult for experts, and it is associated with both objective and subjective reasons. For example, in cases where the circumstances of death are unknown, or there are no medical documents, or they do not contain sufficient information, without which it is impossible to conduct a retrospective clinical and anatomical analysis for the purpose of differential diagnosis between hemolytic shock and post-hemorrhagic anemia. The article deals with the use of new methodological approaches in postmortem morphological diagnostics of blood loss by the rate of its development and its role in thanatogenesis, in forensic medical practice. For example, a particular forensic expertise (case study) shows that the application of two new methods allowed to solve the issues for the investigator related to the cause of death and duration of dying from blood loss. Experts knowledge of new methodological approaches to the forensic diagnosis of acute blood loss will help law enforcement authorities to counteract crimes against the life of citizens, as well as to development the measures to improve the methods for prevention and reduction of mortality from traumatic injuries with blood loss.

17α-Ethinyl estradiol-3-sulfate increases survival and hemodynamic functioning in a large animal model of combined traumatic brain injury and hemorrhagic shock: a randomized control trial

Background Traumatic brain injury (TBI) and severe blood loss resulting in hemorrhagic shock (HS) represent leading causes of trauma-induced mortality, especially when co-occurring in pre-hospital settings where standard therapies are not readily available. The primary objective of this study was to determine if 17α-ethinyl estradiol-3-sulfate (EE-3-SO4) increases survival, promotes more rapid cardiovascular recovery, or confers neuroprotection relative to Placebo following TBI + HS. Methods All methods were approved by required regulatory agencies prior to study initiation. In this fully randomized, blinded preclinical study, eighty (50% females) sexually mature (190.64 ± 21.04 days old; 28.18 ± 2.72 kg) Yucatan swine were used. Sixty-eight animals received a closed-head, accelerative TBI followed by removal of approximately 40% of circulating blood volume. Animals were then intravenously administered EE-3-SO4 formulated in the vehicle at 5.0 mg/mL (dosed at 0.2 mL/kg) or Placebo (0.45% sodium chloride solution) via a continuous pump (0.2 mL/kg over 5 min). Twelve swine were included as uninjured Shams to further characterize model pathology and replicate previous findings. All animals were monitored for up to 5 h in the absence of any other life-saving measures (e.g., mechanical ventilation, fluid resuscitation). Results A comparison of Placebo-treated relative to Sham animals indicated evidence of acidosis, decreased arterial pressure, increased heart rate, diffuse axonal injury and blood–brain barrier breach. The percentage of animals surviving to 295 min post-injury was significantly higher for the EE-3-SO4 (28/31; 90.3%) relative to Placebo (24/33; 72.7%) cohort. EE-3-SO4 also restored pulse pressure more rapidly post-drug administration, but did not confer any benefits in terms of shock index. Primary blood-based measurements of neuroinflammation and blood brain breach were also null, whereas secondary measurements of diffuse axonal injury suggested a more rapid return to baseline for the EE-3-SO4 group. Survival status was associated with biological sex (female > male), as well as evidence of increased acidosis and neurotrauma independent of EE-3-SO4 or Placebo administration. Conclusions EE-3-SO4 is efficacious in promoting survival and more rapidly restoring cardiovascular homeostasis following polytraumatic injuries in pre-hospital environments (rural and military) in the absence of standard therapies. Poly-therapeutic approaches targeting additional mechanisms (increased hemostasis, oxygen-carrying capacity, etc.) should be considered in future studies.

Do alterations in pulmonary vascular tone result in changes in central blood volumes? An experimental study

Background The effects of selective pulmonary vascular tone alterations on cardiac preload have not been previously examined. Therefore, we evaluated whether changing pulmonary vascular tone either by hypoxia or the inhalation of aerosolized prostacyclin (PGI2) altered intrathoracic or pulmonary blood volume (ITBV, PBV, respectively), both as surrogate for left ventricular preload. Additionally, the mean systemic filling pressure analogue (Pmsa) and pressure for venous return (Pvr) were calculated as surrogate of right ventricular preload. Methods In a randomized controlled animal study in 6 spontaneously breathing dogs, pulmonary vascular tone was increased by controlled moderate hypoxia (FiO2 about 0.10) and decreased by aerosolized PGI2. Also, inhalation of PGI2 was instituted to induce pulmonary vasodilation during normoxia and hypoxia. PBV, ITBV and circulating blood volume (Vdcirc) were measured using transpulmonary thermo-dye dilution. Pmsa and Pvr were calculated post hoc. Either the Wilcoxon-signed rank test or Friedman ANOVA test was performed. Results During hypoxia, mean pulmonary artery pressure (PAP) increased from median [IQR] 12 [8–15] to 19 [17–25] mmHg (p < 0.05). ITBV, PBV and their ratio with Vdcirc remained unaltered, which was also true for Pmsa, Pvr and cardiac output. PGI2 co-inhalation during hypoxia normalized mean PAP to 13 (12–16) mmHg (p < 0.05), but left cardiac preload surrogates unaltered. PGI2 inhalation during normoxia further decreased mean PAP to 10 (9–13) mmHg (p < 0.05) without changing any of the other investigated hemodynamic variables. Conclusions In spontaneously breathing dogs, changes in pulmonary vascular tone altered PAP but had no effect on cardiac output, central blood volumes or their relation to circulating blood volume, nor on Pmsa and Pvr. These observations suggest that cardiac preload is preserved despite substantial alterations in right ventricular afterload.

Infusion-transfusion therapy in the treatment of acute massive surgical blood loss in cancer surgery

Введение. Расширенные комбинированные вмешательства являются основным методом лечения пациентов с местнораспространенными солидными злокачественными опухолями. Основным следствием масштабной онкохирургии является риск развития острой массивной кровопотери (ОМОК). Цель исследования: оценка переносимости ОМОК у онкологических больных. Материалы и методы. В одноцентровое ретроспективное исследование с января 1999 г. по декабрь 2018 г. были включены 4236 больных, оперированных в радикальном объёме по поводу злокачественных опухолей различных локализаций, течение операции у которых осложнилось ОМОК. Критерием ОМОК являлась потеря ≥ 50% от расчётного объёма циркулирующей крови (ОЦКр) в течение 3 ч операции. Пациенты, вошедшие в исследование, были разделены на 4 группы в зависимости от объёма кровопотери: от 51 до 100%, от 101 до 200%, от 201 до 300% и свыше 300% ОЦКр. Результаты. Пациенты исследованных групп не различались ни по общим показателям, ни по исходному соматическому статусу. Про анализированы качественный и количественный состав инфузионно-трансфузионной терапии (ИТТ), показатели баланса жидкости интраоперационно, продолжительность пребывания пациентов в отделении реанимации и интенсивной терапии, летальность. Заключение. Соблюдение определенного протокола ИТТ при онкологических операциях, осложнённых ОМОК, является залогом успешного лечения и позволяет снизить интраоперационную летальность до 0,8% и госпитальную летальность до 6,45%. Метод аппаратной реинфузии аутоэритроцитов продемонстрировал высокую эффективность. Background. Cancer surgery remains the backbone of treatment approaches in patients with locally advanced solid malignancies. Risk of acute massive blood loss (AMBL) remains the main complication of such large-scale cancer surgery. Objectives: assessment of AMBL tolerance in cancer patients. Patients/Methods. A single- center retrospective study from January 1999 to December 2018 included 4,236 patients who underwent radical surgery for malignant tumors of various localizations, whose course of surgery was complicated with AMBL. The AMBL criterion was the loss of ≥ 50% of the calculated circulating blood volume (СBVс) within 3 hours of the operation. The patients included in the study were divided into 4 groups depending on the volume of blood loss: from 51 to 100%, from 101 to 200%, from 201 to 300% and over 300% of СBVс. Results. Patients of the studied groups did not differ either in general parameters or in baseline somatic status. The qualitative and quantitative composition of infusion-transfusion therapy (ITT), intraoperative fluid balance, patients stay in the intensive care unit, and mortality were analyzed. Conclusions. Compliance with a specific ITT protocol during cancer surgery complicated by AMBL is the key to successful treatment and allows to reduce intraoperative mortality to 0.8% and hospital mortality to 6.45%. The method of intraoperative red cell salvage and autologus transfusion has demonstrated high efficiency.

Splenomegaly development and disseminated intravascular coagulation syndrome in acute canine babesiosis

Disseminated intravascular coagulation (DIC) syndrome is the main defining process in the pathogenetic axis of complications in canine babesiosis. The involvement of the spleen with further irreversible changes in the organ largely determines the severity of the animal’s condition after spontaneous babesiosis. The work presented here aimed to determine the role of the DIC syndrome as a triggering factor for lesions of the spleen. Clinical and laboratory studies (haematological, biochemical, hemodynamic) have been carried out. Pathological studies of the removed spleen were carried out by histological methods using universal and specific staining. After suffering acute spontaneous babesiosis, the development of hypersplenism and splenomegaly was found in dogs. The diagnosis was confirmed haematologically by the detected cytopenia, normochromic type anaemia. An additional parameter was a significantly increased erythrocyte sedimentation rate. The biochemical profile indicated the development of bilirubinaemia due to the conjugated fraction, hyperfermentation of transaminases, hypoalbuminemia, which reflected the development of hepatitis and liver failure. Markers of DIC syndrome in laboratory studies are represented by reliable hypofibrinogenemia, increased level of fibrinogen/fibrin degradation products, including D-dimer, and soluble fibrin monomer complexes. The multidirectional indices of coagulation tests (activated partial thromboplastin and prothrombin time) made it possible to classify the stage of “consumption coagulopathy” of the DIC syndrome. The haemodynamic parameters of the sick dogs were characterized by a significant deficit in the circulating blood volume. Together with the indicators of the “consumption coagulopathy” stage of the DIC syndrome, the hemodynamic indexes indicate a moderate degree of shock stage II – the stable reversibility, but the magnitude of the circulating blood volume deficit determines the tendency towards shock irreversibility. Histological studies have established a significant proliferation of the stromal elements of the organ, the formation of specific complexes of vessels with sinuses, clogging with blood clots, and the organ's parenchyma dystrophy. Such changes characterize complete splenomegaly, which is based on the organo-pathology of the DIC syndrome. The deposition of “old” fibrin in the connective tissue structures of the spleen indicates that DIC syndrome continues throughout the entire period of hyperplastic changes in the organ. The presence of hyalinosis in blood vessel walls of the spleen parenchyma determines irreversible changes in them. Thus, DIC syndrome is the basis for splenomegaly development in dogs after acute spontaneous babesiosis. It is confirmed by laboratory blood tests and histologically by the presence of fibrin thrombi in the structures of the organ, which determine the organopathology of the syndrome. The information obtained serves to expand the concepts of the pathogenesis of blood protozoal disease, define the high risk of complications that can become fatal for the health and life of animals.

SPECIFICITY OF USING TRANEXAMIC ACID IN PATIENTS WITH CARDIAC SURGERY

Objective. To evaluate the efficacy of tranexamic acid (TA) in cardiac surgery patients undergoing the open-heart surgery under conditions of artificial blood circulation (ABC) by determining the volume of perioperative blood loss using the hemoglobin balance method. Methods. A pilot non-randomized prospective clinical trial was conducted. To determine the effectiveness of TA use, 2 groups of patients were formed: the 1^st group, without TA application (n=40), the 2^nd group - with TA application intraoperatively (n=40). In group 2, prior to sternotomy, intravenous bolus injection of TA (1000 mg (20 ml of 5% solution)) was performed and further titration of TA through a syringe dispenser was continued at a rate of 4 ml/hour (200 mg/hour) until the end of the operation.The volume of intraoperative blood-loss was assessed by the hemoglobin balance method. A special protocol was developed to control the volume of postoperative blood loss. Results. The volume of circulating blood (VCB) calculated by Nadler’s formula for the first group was 5433.2 (5008.5; 5768.2) ml, for the second - 5214.0 (4944.1; 5546.8) ml. In the first group of patients who did not receive TA during open- heart surgery, the volume of blood loss was 1460.6 (1196.8; 1725.8) ml or 26.9 % of the average circulating blood volume (CBV), and in the second group of patients who received TA intraoperatively - 1090.7 (882.3; 1468.6) ml or 20.9% of the CBV (p<0,001). Conclusion. The application of TA in cardiac surgery patients during open-heart surgery with ABC according to the developed algorithm (1000 mg/bolus, titration during surgery-200 mg/h) for the purpose of blood saving the volume of blood-loss was reduced by 25.3% compared to the control group. What this paper adds Algorithm for the use of tranexamic acid to reduce perioperative blood loss in cardiac surgery using cardiopulmonary bypass (CPB) during open-heart surgery has been developed. This algorithm included intravenous tranexamic acid injection (1,000 mg.) followed by titration during the operation - 200 mg/h). The use of this algorithm in cardiac surgical procedures allows reducing the volume of blood loss by 25.3%.

Non-immune fetal hydrops in late pregnancу: antenatal ultrasound monitoring and pregnancy outcomes in a series of 14 cases

Background. Fetal hydrops is the accumulation of extracellular fluid in two or more fetal cavities, often in combination with subcutaneous edema. An isolated accumulation of fluid only in the abdominal, pleural, or pericardial cavities is described as ascites, pleural effusion (hydrothorax), pericardial effusion (hydropericardium). Features of the pathogenesis of non-immune hydrops fetalis (NIHF) are the follow: high hydrophilicity of fetal tissues, obstruction of the lymphatic vessels, impaired lymph return, congestive heart failure, obstruction of venous return, changes in fetal venous pressure. All these factors lead to the release of fluid from cells and tissues into the «third» spaces – the abdominal, thoracic, pericardial cavities, as well as the subcutaneous space. The oncotic pressure of fetal plasma proteins is not of great importance in the formation of the fetal circulating blood volume. Currently, all the links in the pathogenesis of hydrops fetalis syndrome with various etiological factors are not fully known. The prevalence of NIHF is unknown because it is difficult to collect relevant data; many cases of the disease are not diagnosed until intrauterine fetal death or may spontaneously resolve during the prenatal period. Currently, up to 90% of all cases of fetal dropsy are attributed to NIHF. Purpose – acquaintance of the medical community with the diagnosis and treatment of non-immune hydrops as well as the analysis of clinical features, ultrasound monitoring and perinatal outcomes of 14 cases of non-immune fetal hydrops onset in a second half of pregnancy. Materials and methods. The material for the study were publications and results of clinical trials found in the databases Scopus, Web of Science Core Collection and PubMed for the period 2009–2020 and the analytic report of the own series of 14 cases of non-immune hydrops fetalis (NIHF) of various origins. During the period of 2005–2020 under the supervision in the Ultrasound Department of Kharkiv regional hospital with regional perinatal center there were 14 pregnant women with NIHF diagnosed in a second half of pregnancy. Clinical features are described, ultrasound images and Doppler monitoring are given, perinatal / postnatal results are studied. Results and discussion. The analysis of clinical features, ultrasound monitoring and pregnancy outcomes of 14 cases of non-immune fetal hydrops developed in the second half of pregnancy in presented series was carried out. 6/14 fetuses had structural anatomical defects (lung sequestration, СDH, myasthenia gravis, megacystis and hydronephrosis, epidermolysis bullosa, meconium peritonitis, intestinal atresia). Mortality rate (including perinatal and infant losses) was as high as 9/14 cases (64.2%): 3 of antenatal, 4 of neonatal, 2 of infant death). Surgical treatment was performed on 2 newborns. 5 newborns had apparently a favorable clinical postnatal outcome. In 2 cases, spontaneous resolution with complete regression of hydrops was observed (parvovirus-B19 and idiopathic NIHF). Complete recovery of fetus (spontaneous regression of hydrops without any deterioration and pathological consequences) was observed in 1 case. Conclusions. Antenatal ultrasound monitoring of fetus with NIHF is based on the assessment of PSV CMA, ductus venous, umbilical vein, atrioventricular flow. According to the results of the study, it was revealed that the cardiovascular profile of the fetus with NIHF is disturbed earlier, and the placental profile and arterial Doppler-later. Normal umbilical artery Doppler do not exclude the possibility of an adverse outcome, including intrauterine fetal demise. Extended Doppler monitoring is essential at NIHF. All neonates with NIHF in an antenatal anamnesis require postnatal follow-up.

Safety and utility of modified ultrafiltration in pediatric cardiac surgery

Introduction: Modified ultrafiltration (MUF) is employed at the termination of cardiopulmonary bypass (CPB) in pediatric and neonatal patients undergoing congenital heart surgery to reduce the accumulation of total body water thus increasing the concentration of red blood cells and the other formed elements in the circulation. Modified ultrafiltration has been reported to remove circulating pro-inflammatory mediators that result in systemic inflammatory response syndrome (SIRS) postoperatively. Methods: Four hundred patients undergoing cardiac surgery requiring cardiopulmonary bypass and weighing less than or equal to 12 kg were retrospectively evaluated for the effectiveness of MUF. After the termination of CPB, blood was withdrawn through the aortic cannula and passed through a hemoconcentrator attached to the blood cardioplegia set and returned to the patient through the venous cannula. The entire CPB circuit volume in addition to the patient’s circulating blood volume were concentrated until the hematocrit value displayed on the CDI cuvette within the MUF circuit reached 45% or there was no more volume to safely remove. At the same time a full unit of FFP can be infused as water is being removed, thus maintaining euvolemia. Results: MUF was performed in all 400 patients with no MUF-related complications. Following the conclusion of MUF, anecdotal observations included improved surgical hemostasis, improved hemodynamic parameters, decreased transfusion requirements, and decreased ventilator times. Conclusions: Complete MUF enables the clinician to safely raise the post-CPB hematocrit to at least 40% while potentially removing mediators that could result in SIRS. In addition a full unit of FFP can be administered while maintaining euvolemia.